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Association of several loci of SMAD7 with colorectal cancer: A meta-analysis based on case-control studies
Qiang Xiao1, Jian Chen, Jia Zhu
1General Surgery Department, First Affiliated Hospital of Nanchang University, Jiangxi, China.
Background:
Sma-and mad-related protein 7 (SMAD7) can affect tumor progression by closing transforming growth factor-beta intracellular signaling channels. Despite the extensive research on the correlation between SMAD7 polymorphisms and colorectal cancer (CRC), the conclusions of studies are still contradictory. We conducted a study focusing on the association of SMAD7 polymorphisms rs4939827, rs4464148, and rs12953717 with CRC.
Methods:
We searched through 5 databases for articles and used odd ratios (ORs) and 95% confidence intervals (CIs) to discuss the correlation of SMAD7 polymorphisms with CRC risk. The heterogeneity will be appraised by subgroup analysis and meta-regression. Contour-enhanced funnel plot, Begg test and Egger test were utilized to estimate publication bias, and the sensitivity analysis illustrates the reliability of the outcomes. We performed False-positive report probability and trial sequential analysis methods to verify results. We also used public databases for bioinformatics analysis.
Results:
We conclusively included 34 studies totaling 173251 subjects in this study. The minor allele (C) of rs4939827 is a protective factor of CRC (dominant, OR/[95% CI] = 0.89/[0.83-0.97]; recessive, OR/[95% CI] = 0.89/[0.83-0.96]; homozygous, OR/[95% CI] = 0.84/[0.76-0.93]; heterozygous, OR/[95% CI] = 0.91/[0.85-0.97]; additive, OR/[95% CI] = 0.91/[0.87-0.96]). the T allele of rs12953717 (recessive, OR/[95% CI] = 1.22/[1.15-1.28]; homozygous, OR/[95% CI] = 1.25/[1.13-1.38]; additive, OR/[95% CI] = 1.11/[1.05-1.17]) and the C allele of rs4464148 (heterozygous, OR/[95% CI] = 1.13/[1.04-1.24]) can enhance the risk of CRC.
Conclusion:
Rs4939827 (T > C) can decrease the susceptibility to CRC. However, the rs4464148 (T > C) and rs12953717 (C > T) variants were connected with an enhanced risk of CRC.
Insights
The SMAD7 rs4939827 polymorphism may decrease colorectal cancer risk, while rs4464148 and rs12953717 polymorphisms are associated with an increased risk of CRC.
Area of Science:
- Genetics
- Oncology
- Molecular Biology
Background:
- Sma-and mad-related protein 7 (SMAD7) influences tumor progression by regulating transforming growth factor-beta signaling.
- Previous studies on SMAD7 polymorphisms and colorectal cancer (CRC) risk have yielded conflicting results.
Approach:
- A meta-analysis was conducted on 34 studies involving 173,251 participants.
- Statistical methods including odds ratios (ORs), 95% confidence intervals (CIs), subgroup analysis, meta-regression, and bias assessment were employed.
- Bioinformatic analyses were performed using public databases.
Key Points:
- The minor allele (C) of SMAD7 rs4939827 was found to be a protective factor against CRC across various genetic models.
- The T allele of rs12953717 and the C allele of rs4464148 were associated with an increased risk of CRC.
- Sensitivity, publication bias, and False-positive report probability analyses confirmed the reliability of the findings.
Conclusions:
- SMAD7 rs4939827 polymorphism (T > C) is linked to reduced susceptibility to colorectal cancer.
- Conversely, SMAD7 rs4464148 (T > C) and rs12953717 (C > T) variants are associated with an elevated risk of developing CRC.
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